The study of hyoscyamine in oxidative stress of liver cells in male rat

Background and aims: Increased production of free radicals by endogenous systems and exogenous sources in cells leads to oxidative stress, which damages to the cells of various organs. Hyoscyamine is one of the important tropane alkaloid isolated from some Solanaceous species used to traditional medicine that they are used for their analgesic, anti-inflammatory, antipyretic, and anticonvulsant activities. The antioxidant and antiglycation properties of tropane alkaloids may represent a role in dealing with oxidative stress. The aim of this study was to investigate the antioxidant and antiglycation effects of hyoscyamine component on the liver cells in male rats. Methods: In this experimental- laboratory study, liver cells were isolated from male Sprague–Dawley rats. The cells cultured under standard conditions. Various concentrations of hyoscyamine (0-32 µM) were treated on rat liver cells. Then, the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) as well as glyoxal and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition were measured by spectrophotometry. High-performance liquid chromatography (HPLC) was performed for measuring malondialdehyde (MDA) in liver cells. Results: CAT, SOD and GPX enzyme activities increased as the concentration of hyoscyamine increased. DPPH showed a strong inhibition on reactive oxygen species generation compared to control group. The amount of SOD, CAT and GPX enzyme activities in 8 micromolar concentration of hyoscyamine compared with the control group significantly increased as 10.33 and 8.6 and 6.3 units (P<0.05). Also, hyoscyamine (4µM) reduced the amount of MDA, glyoxylate and DPPH compared to the control group as 1.94, 2.26, and 2.33 times (P<0.05). Conclusion: Our findings indicated that hyoscyamine had considerable antioxidant and antiglycation activities on rat liver cells. This compound protects liver cells against the damaging effects of free radicals. The effects of this compound for the treatment of diseases associated with oxidative stress would be useful in the future

Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation of H19 Noncoding RNA in Ovarian A2780 Cells

Abstract Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders. In addition, this drug may display its effects through regulation of noncoding RNAs controlling gene expression. The aim of the present study was the investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the relation of the H19 levels with apoptosis and cisplatin resistance. Briefly, treatment with VPA not only led to significant increase in apoptosis rate, but also increased the cisplatin sensitivity of A2780/CP cells. We found that following VPA treatment, the expression of H19 and EZH2 decreased, but the expression of p21 and PTEN increased significantly. To investigate the involvement of H19 in VPA-induced apoptosis and cisplatin sensitivity, H19 was inhibited by a specific siRNA. Our results demonstrate that H19 knockdown by siRNA induced apoptosis and sensitized the A2780/CP cells to cisplatin-induced cytotoxicity. These data indicated that VPA negatively regulates the expression of H19 in ovarian cancer cells, which subsequently leads to apoptosis induction, cell proliferation inhibition, and overwhelming to cisplatin resistance. The implication of H19→EZH2→p21/PTEN pathway by VPA treatment suggests

Effect of valproic acid on cisplatin-resistant ovarian cancer cell lines

Background and aims: Platinum resistance has been one of the most important problems in the management of ovarian cancer. The effects of various chemotherapeutic agents are limited in patients with platinum resistance. Therefore, developing new anticancer drugs that can improve the effect of currently used cytostatics is critical. The current study investigated the effects of valproic acid (VPA) alone and in combination with cisplatin on ovarian cancer cells. Methods: In this experimental study, the human ovarian cancer cell lines (A2780-S and A2780-CP) were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated with various concentrations of cisplatin (0.15-400 µg/mL) or VPA (10-2000 µg/mL) and were incubated for 24, 48, and 72 hours. Moreover, A2780 cells were co-treated with different concentrations of cisplatin and VPA for 48 hours. Afterward, cell viability was investigated using MTT assay. GraphPad Prism statistical software was used for the data analysis and ANOVA and Duncan’s test were conducted. Results: A dose- and time-dependent reduction was observed in cell viability following the treatment with cisplatin or VPA. Moreover, cotreatment of the A2780 cells with cisplatin and VPA resulted in a significantly greater inhibition of cell viability compared to the treatment with either agent alone. Conclusion: Overall, it can be argued that VPA does not only cause inhibition of proliferation and induction of apoptosis in ovarian cancer cells but also helps to enhance the antiproliferative effects of cisplatin and results in the increased susceptibility to cisplatin in resistant cells. VPA may therefore be used to treat cancer in the future. Keywords: Ovarian cancer, Cisplatin, Valproic acid, Platinum resistance, Antiproliferative effec

Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation of H19 Noncoding RNA in Ovarian A2780 Cells

Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders. In addition, this drug may display its effects through regulation of noncoding RNAs controlling gene expression. The aim of the present study was the investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the relation of the H19 levels with apoptosis and cisplatin resistance. Briefly, treatment with VPA not only led to significant increase in apoptosis rate, but also increased the cisplatin sensitivity of A2780/CP cells. We found that following VPA treatment, the expression of H19 and EZH2 decreased, but the expression of p21 and PTEN increased significantly. To investigate the involvement of H19 in VPA-induced apoptosis and cisplatin sensitivity, H19 was inhibited by a specific siRNA. Our results demonstrate that H19 knockdown by siRNA induced apoptosis and sensitized the A2780/CP cells to cisplatin-induced cytotoxicity. These data indicated that VPA negatively regulates the expression of H19 in ovarian cancer cells, which subsequently leads to apoptosis induction, cell proliferation inhibition, and overwhelming to cisplatin resistance. The implication of H19 -> EZH2 -> p21/PTEN pathway by VPA treatment suggests that we could repurpose an old drug, valproic acid, as an effective drug for treatment of ovarian cancer in the future